Synthetic silica as packing material in supported liquid extraction

ABSTRACT

In embodiments, a packing material for supported liquid extraction has a sorbent media that includes synthetic silica particles. In embodiments, the synthetic silica particles can have physical properties relating to one or more of particle surface area, shape, size, or porosity. In one embodiment, synthetic silica particles have a surface area less than about 30 m 2 /g. In another embodiment, the synthetic silica particles have an approximately uniform particle shape. In further examples, synthetic silica particles have a particle size in a range of about 30-150 μm inclusive or greater than about 200 μm. In another embodiment, synthetic silica particles are arranged to have a pore size greater than about 500 Angstroms. In an embodiment, an apparatus for supported liquid extraction includes a container and a sorbent media that includes synthetic silica particles. In a further embodiment, a method for extracting target analytes through supported liquid extraction is provided.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit of U.S. provisional patentapplication, Appl. No. 62/657,532, filed Apr. 13, 2018, incorporated inits entirety herein by reference.

TECHNICAL FIELD

The present disclosure relates generally to the field of samplepreparation.

BACKGROUND

Liquid extraction uses relative solubility differences to separatechemical substances from one liquid phase (solvent) into another priorto chemical analysis. Two major types of liquid extraction areLiquid-Liquid Extraction (LLE) and Supported Liquid Extraction (SLE).SLE uses a bed of packing material also referred to as a SLE stationaryphase or packing bed. The packing material is placed into a container,such as, a cartridge, column, or well of a 96-well plate.

In one known SLE procedure, an aqueous sample containing analytes isloaded into a SLE container having a packing bed. The packing bedabsorbs the sample and spreads it throughout the bed by capillaryaction. This creates a thin film over the surface area of the packingbed material. To extract analytes of interest, an appropriate organicsolvent is introduced into the container to percolate through thepacking bed and contact the thin film of aqueous sample. Analytes ofinterest transfer from the aqueous sample into the organic solvent andare eluted from the container and collected. Water and unextractedimpurities remain in the stationary phase. The eluted analytes can thenbe exchanged into a more suitable solvent for analysis or injecteddirectly depending on the type of detection to be used.

Compared to conventional LLE methods, the SLE approach offers manyadvantageous features including better reproducibility, lower solventconsumption, elimination or minimization of hazardous solvents, theelimination of emulsions, and is amenable to high-throughput workflows(i.e. automation). The technique of SLE has been widely applied inpharmaceutical industries, forensic chemistry, and environmentalanalysis.

The success of SLE extraction relies on the quality of the stationaryphase materials. Ideally the stationary phase should provide aconsistent flow pattern, high cleanliness, comparable or betterperformance as LLE, and low cost. Conventionally, the packing materialused in SLE devices is diatomaceous earth, which is a naturallyoccurring material composed mostly of silica. Although diatomaceousearth is cost-effective it suffers from a series of issues includinglot-to-lot variation in particle morphology, shape and unwantedimpurities. Additionally, low levels of crystalline silicon dioxideincurred in diatomaceous earth may present occupational health risks toworkers' including silicosis and carcinogenicity necessitating strictregulatory controls in manufacturing environments. There is a need foralternative packing materials for SLE methods that can provide superiormaterial consistency, cleanliness, cost effectiveness, and with lesshealth concerns.

A synthetic sorbent different from the present disclosure has been madeavailable by Phenomenex (Torrance, Calif.) currently referred to as aSLE product, Novum™. Unlike conventional SLE products based ondiatomaceous earth, the Novum™ product appears to use a synthetic SLEsorbent for both SLE tubes and 96 well plates.

OVERVIEW

The inventors recognized what is needed is an improved and safer packingmaterial for SLE compared to conventional diatomaceous earth SLEproducts. The inventors also recognized that improvements were needed inSLE packing materials having synthetic silica.

In embodiments, a packing material for supported liquid extraction has asorbent media that includes synthetic silica particles. In embodimentsthe synthetic silica particles can be fine tuned to have particularphysical properties relating to one or more of particle surface area,shape, size, or porosity.

In one embodiment, synthetic silica particles have a surface area lessthan about 30 m²/g.

In a further embodiment, the synthetic silica particles have anapproximately uniform particle shape. In an example, an approximatelyuniform particle shape is an approximately spherical shape having anapproximately uniform diameter across a distribution of the particles.

In a further embodiment, synthetic silica particles have a particle sizein a range of about 30-150 μm inclusive.

In a further embodiment, synthetic silica particles have a particle sizegreater than about 200 μm.

In a further embodiment, synthetic silica particles are arranged to havea pore size greater than about 500 Angstroms.

In further embodiments, the synthetic silica particles can include atleast one of Agilent SLE materials 1, 2, or 3.

In another embodiment, an apparatus for supported liquid extractionincludes a container and a sorbent media. The sorbent media ispositioned within the container for use as a stationary phase insupported liquid extraction. The sorbent media includes synthetic silicaparticles.

In a further embodiment, a method for extracting target analytes throughsupported liquid extraction is provided. The method includes positioningsorbent media in a container, wherein the sorbent media includessynthetic silica particles having a surface area less than about 30 m²/gand an approximately uniform particle shape. The method can also includeloading an aqueous sample onto the sorbent media, and equilibrating theloaded sample and the sorbent media to obtain a layer of the aqueoussample on the synthetic silica particles. Further steps include elutingthe obtained aqueous sample layer on the synthetic silica particles withorganic solvent to extract target analytes, and outputting the extractedtarget analytes for analysis.

In a further embodiment, the synthetic silica particles have a particlesize of less than about 150 μm, and the method includes applying apositive pressure or vacuum to initiate a flow of the aqueous samplethrough the synthetic silica media at a consistent flow rate. In anotherembodiment, the synthetic silica particles have a particle size greaterthan about 200 μm, and the method includes initiating with gravity aflow of the aqueous sample through the sorbent media at a consistentflow rate.

Further embodiments, features, and advantages of the invention, as wellas the structure and operation of the various embodiments of theinvention are described in detail below with reference to accompanyingdrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated into and constitute apart of this specification, illustrate one or more examples ofembodiments and, together with the description of example embodiments,serve to explain the principles and implementations of the embodiments.

FIG. 1 is a diagram of an apparatus having synthetic silica for use as astationary phase in SLE according to an embodiment.

FIG. 2 is flowchart diagram of a method for extracting target analytesthat includes using synthetic silica as a stationary phase in SLEaccording to an embodiment.

FIG. 3 is diagram illustrating aspects of the method of FIG. 2 accordingto an embodiment.

FIG. 4 shows Scanning Electronic Microscopic (SEM) Images of Agilent SLEmaterial 1 used for SLE under 100× magnification according to anembodiment.

FIG. 5 shows Scanning Electronic Microscopic (SEM) Images of Agilent SLEmaterial 2 used for SLE under 25× magnification according to anembodiment.

FIG. 6 shows Scanning Electronic Microscopic (SEM) Images of Agilent SLEmaterial 3 used for SLE under 50× magnification according to anembodiment.

FIG. 7 shows Scanning Electronic Microscopic (SEM) Images of acompetitive SLE product under 50× magnification in an analysis carriedout by inventors.

DESCRIPTION OF EXAMPLE EMBODIMENTS

Example embodiments are described herein in the context of samplepreparation and in particular with respect to containers andapplications involving supported liquid extraction (SLE). Embodimentsdescribed here include a sorbent media having synthetic silica particlesfor SLE. Embodiments include packing materials and apparatuses for SLE,and methods for extracting target analytes through supported liquidextraction (SLE).

The inventors identified several features and parameters that can beused in preferred embodiments of the sorbent media having syntheticsilica particles for SLE. First, synthetic silica particles with lowsurface area (less than about <30 m²/g) and large pore size (greaterthan about >500 Å) provide an ideal SLE performance in an embodiment.Second, for vacuum or positive pressure flow initiation, particle sizesshould be in the range of about 30-150 microns to ensure a consistenteluent flow at a rate that gives efficient analyte extraction withoutthe need for high vacuum or pressure. For gravity flow initiation, theparticle size should be larger than about 200 microns to ensureacceptable flow rates. The synthetic silica particles should be of highcleanliness to avoid the introduction of impurities that can lead toanalytical variability.

Those of ordinary skill in the art will realize that the followingdescription is illustrative only and is not intended to be in any waylimiting. Other embodiments will readily suggest themselves to suchskilled persons having the benefit of this disclosure. Reference willnow be made in detail to implementations of the example embodiments asillustrated in the accompanying drawings. The same reference indicatorswill be used to the extent possible throughout the drawings and thefollowing description to refer to the same or like items.

In the detailed description of embodiments that follows, references to“one embodiment”, “an embodiment”, “an example embodiment”, etc.,indicate that the embodiment described may include a particular feature,structure, or characteristic, but every embodiment may not necessarilyinclude the particular feature, structure, or characteristic. Moreover,such phrases are not necessarily referring to the same embodiment.Further, when a particular feature, structure, or characteristic isdescribed in connection with an embodiment, it is submitted that it iswithin the knowledge of one skilled in the art to effect such feature,structure, or characteristic in connection with other embodimentswhether or not explicitly described.

Synthetic Silica Packing Material for SLE

In an embodiment, a sorbent media having synthetic silica particles isused as a packing material. For example, a sorbent media made up ofsynthetic silica particles can be used as a stationary phase material inSLE. In embodiments, as described further below, synthetic silicaparticles can be used having particular physical properties includingsurface area, shape, particle size, or porosity. Using synthetic silicaparticles as described herein overcomes disadvantages of other known SLEbed materials and allows more control of physical properties of thepacking material to improve SLE sample preparation.

The inventors found a number of further examples with particularphysical properties that are advantageous. In one example, with respectto particle surface area, a sorbent media includes synthetic silicaparticles having a surface area less than about 30 m²/g.

In a further feature, the synthetic silica particles have anapproximately uniform particle shape. For example, the approximatelyuniform particle shape can be approximately spherical shape and have anapproximately uniform diameter across a distribution of the particles.The approximately uniform particle shape can also be rounded in oblong,ovals or other rounded shapes without shards, sharp, pointed or jaggededges.

Further embodiments relate to particle sizes. In one example, thesynthetic silica particles have a particle size in a range of about30-150 μm inclusive. In another example, synthetic silica particles havea particle size greater than about 200 μm.

In a further feature, porosity of the synthetic silica particles isconsidered. In one example, the synthetic silica particles are arrangedto have a pore size greater than about 500 Angstroms (Å).

Finally, in examples, the inventors developed three types of syntheticsilica particles manufactured by Agilent Technologies Inc., and referredto herein as Agilent SLE material 1, 2, or 3. These three types ofsynthetic silica particles have different particle size distributionsfrom one another. The first type, noted as Agilent SLE material 1 in thefollowing context, has relatively small particle size (less than 150 μm)and requires positive pressure or vacuum to initiate flow of liquidthrough the sorbent bed. The second type, noted as Agilent SLE material2 in the following context, has a larger particle size (greater than 600μm) and supports flow of liquids under gravity (gravity flow without theneed of positive pressure or vacuum manifold). A third type, noted asAgilent SLE material 3 has particle size 300 μm and also supports eluentflow under gravity.

FIG. 4 shows Scanning Electronic Microscopic (SEM) Images of Agilent SLEmaterial 1 used for SLE under 100× magnification according to anembodiment. FIG. 5 shows Scanning Electronic Microscopic (SEM) Images ofAgilent SLE material 2 used for SLE under 25× magnification according toan embodiment. FIG. 6 shows Scanning Electronic Microscopic (SEM) Imagesof Agilent SLE material 3 used for SLE under 50× magnification accordingto an embodiment.

In contrast, FIG. 7 shows Scanning Electronic Microscopic (SEM) Imagesof competitor SLE sorbent under 50× magnification in an analysis carriedout by inventors. The competitive SLE sorbent shown comprises a sampleobtained from Phenomenex (Torrance, Calif.) referred to as a SLE productnamed, Novum™.

Additional material description and characterization of these AgilentSLE material 1, 2, and 3 silica particles is described further belowwith respect to a comparison analysis carried out by the inventors. Thecomparison analysis compares Agilent SLE material 1, 2, and 3 from acompetitive SLE sorbent.

Further Advantages and Features

The inventors recognized further advantages to synthetic silicaparticles as described herein. The inventors recognized the physicalproperties of the synthetic silica such as particle size, surface area,and/or porosity can be easily tuned by adjusting the syntheticparameters when different SLE characteristics are desired.

The inventors identified several advantages for synthetic silicaexamples over traditional diatomaceous earth for SLE workflows:

-   -   Comparable or better extraction performance in terms of analyte        recovery, reproducibility, and flow consistency;    -   High cleanliness to minimize introduction of impurities that may        produce analytical variability;    -   Easy adjustment of physiochemical properties including particle        size, surface area, and pore size;    -   A reliable synthetic process allows for stringent quality        control;    -   The synthesis is fast, simple, scalable, and low price; and

This disclosure further provides multiple sorbent media specificationsto support workflows with vacuum, positive pressure and gravity.

Further description of synthetic packing material for SLE andapplications therefor that can be used in further embodiments will nowbe described with respect to an SLE apparatus and method for extractinganalytes.

Apparatus for SLE

FIG. 1 is a diagram of an apparatus 100 having synthetic silica for useas a stationary phase in SLE according to an embodiment. Apparatus 100includes a container 110 removably coupled to a collection vial 130. Asorbent media 120 is positioned within container 110 for use as astationary phase in supported liquid extraction. Sorbent media 120includes synthetic silica particles as described herein. First andsecond layers of porous frit composition 115 and 125 respectively, arepositioned within the container on opposite sides of sorbent media 120.Container 110 can have an opening on one end to receive a sample.Collection vial 130 can be arranged at another end of container 110 andconfigured to receive analytes extracted from an eluted sample passedthrough container 110.

In examples, the mass, particle size, and surface area of the syntheticsilica particles in sorbent media 120 determine a loading capacity withan aqueous sample. According to one feature, SLE performance (recoveryand precision) can be at least comparable to LLE.

This embodiment is illustrative and not intended to be limiting.Container 110 for example can be a tube, cartridge, well in a wellplate, or other type of container suitable for SLE. Porous frit layers115, 125 can be any type of porous frit including but not limited to agranulated glass, polymeric, and/or ceramic composition. Porous fritlayers 115, 125 are also optional and can be omitted. Other materials orlayers may also be used on either side of sorbent media 120 dependingupon a particular SLE application as would be apparent to a personskilled in the art given this description. Collection vial 130 is alsooptional and other receptacles or tubing can be used to collect or passan output sent through container 110.

Examples of the use of apparatus 100 to extract analytes of interest asin drug testing or other types of analysis is described further belowwith respect to FIGS. 2-3.

Method for Extracting Target Analytes

FIG. 2 is flowchart diagram of a method 200 for extracting targetanalytes that includes using synthetic silica as a stationary phase inSLE according to an embodiment (steps 210-260). In many examples used insample preparation, an aqueous sample may include the analytes ofinterest to be extracted. Examples of an aqueous sample that may be usedinclude but are not are not limited, blood, plasma, urine, saliva,water, or sweat. These samples may be used in drug testing for examplewhen the analytes of interest indicate the presence of drugs, controlledsubstances or other chemicals in the samples. These examples areillustrative and not intended to be limiting. Other samples may be usedin different applications to detect analytes of interest inpharmaceutical, forensic chemistry, environmental analysis or other SLEapplications.

For brevity, method 200 will be described with reference to apparatus100 but is not necessarily intended to be limited to this specificapparatus or example.

As shown in FIG. 2, method 200 includes positioning sorbent media in acontainer as a stationary phase for SLE (step 210). Sorbent mediaincludes synthetic silica particles as described herein. The containercan be a container 110 as described with respect to FIG. 1.

Sample preparation may also require first pretreating a sample (step220). This is optional in that some aqueous samples may also not requirepretreating the sample.

In step 230, an aqueous sample having analytes of interest is loadedonto sorbent media. FIG. 3 for example shows a diagram A of an aqueoussample 302 loaded onto sorbent media 304 having synthetic silicaparticles. Aqueous sample 302 as used here refers to an aqueous samplewith or without optional pretreating.

An equilibrating step is carried out (step 240) to obtain a layer of theaqueous sample on the synthetic silica particles. For example, theaqueous sample may be allowed to soak into the stationary phase. Asshown in diagram B in FIG. 3, the loaded sample and sorbent media areequilibrated on the synthetic silica particles.

Next, elution is carried out (step 250). In particular, the aqueoussample layer on the synthetic silica particles is eluted with an organicsolvent to extract target analytes. For example, a water immiscibleorganic solvent can be passed through the sorbent media 304 stationaryphase to extract analytes of interest to be collected for analysis. Asshown in FIG. 3, the eluting removes analytes of interest.

In step 260, the extracted analytes of interest are outputted foranalysis. For example, they can be output to a receptacle for collectionas shown in diagram C in FIG. 3. In one embodiment, the synthetic silicaparticles have a particle size of less than about 150 μm, and theoutputting includes applying a positive pressure or vacuum to initiate aflow of the aqueous sample through the synthetic silica media at aconsistent flow rate. Initiating with gravity is also contemplated. Inanother embodiment, the synthetic silica particles have a particle sizegreater than about 200 μm, and the outputting includes initiating withgravity a flow of the aqueous sample through the sorbent media at aconsistent flow rate.

Example Analytical Results and Discussion Relative to LLE

The inventors further performed an analysis comparing the results of LLEextraction and three lots of synthetic silica particles. The three lotsof synthetic silica particles represented examples of each of respectiveAgilent SLE materials 1, 2, and 3. The Agilent SLE material 1, 2, and 3were compared to LLE in this evaluation analysis and demonstratedacceptable performance of the SLE synthetic silica materials when usedin an example SLE workflow.

In the analysis for testing purposes, a SLE sample preparation of humanplasma was spiked with a 10 ng/mL drug of abuse mixture. Performances ofthe three SLE stationary phases were tested by spiking a mixture of 24common drugs of abuse into human plasma and conducting the SLE protocol.Percent recovery was determined using pre-spiked plasma samples at 10ng/mL and blank plasma samples post-spiked at 10 ng/mL. Both pre-spikedand blank plasma samples were diluted 1:1 (V/V) with 0.5 M ammoniumhydroxide and mixed. Next, 400 μL of diluted plasma was loaded onto thestationary phase in a 3 cc cartridge. Vacuum was applied, as necessary,to pull the sample into the bed. The sample was allowed to equilibratefor 5 min before eluting with MTBE (2×2 mL). The collected eluent wasevaporated to dryness and reconstituted with 200 μL of 85:15 (V/V) 5 mMammonium formate+0.1% formic acid:acetonitrile. The samples were theninjected onto an Agilent 1290LC/6490 QQQ liquid chromatography/massspectrometer (LC/MS) system for analysis using a multiple reactionmonitoring (MRM) method for quantitation.

As shown in FIG. 3, picture A and B, the sample being tested was loadedand allowed to “equilibrate” on the SPE stationary phase for severalminutes before elution to allow the formation of a thin aqueous layerfor subsequent extraction. After 5 min, a water immiscible organicsolvent (DCM, ethyl acetate, hexane, MTBE, etc.) was passed through thestationary phase to extract the analytes of interest. The aqueous phaseremains in the cartridge while the organic extract is collect in asecondary vessel for analysis (picture C).

Table 1 summarizes the results of a LLE extraction using MTBE and 3silica materials in an SLE workflow. Recovery (% Rec.) andreproducibility (% RSD) is shown for the 24 analytes with respect to thestationary phase. Analyte recovery is used to access material andworkflow suitability, where 100% recovery indicates ideal performance.The % RSD measures method and material consistency and a range of 0-20is acceptable. Bed masses were optimized for each synthetic silicamaterial by measuring aqueous holding capacity with respect to bed massusing the protocol described with respect to FIG. 3. For the resultsshown in this example, 3 cc tubes contain 0.50 g Agilent SLE Material 1,0.60 g Agilent SLE material 2, and 0.50 g Agilent SLE material 3.

TABLE 1 Agilent SLE Agilent SLE Agilent SLE LLE (MTBE) Material 1Material 2 Material 3 % Rec. % RSD % Rec. % RSD % Rec. % RSD % Rec. %RSD Codeine 89.1 4.5 107.0 2.5 83.0 11.0 90.8 3.5 Oxycodone 87.2 24.598.5 6.7 81.2 8.0 82.9 4.7 Amphetamine 79.8 0.6 100.2 4.0 76.0 6.2 90.42.3 MDA 82.0 4.3 102.9 4.2 90.9 3.4 87.7 4.3 Hydrocodone 83.9 0.9 96.23.0 78.7 9.9 87.1 4.4 MDMA 64.2 27.6 97.4 3.6 89.2 4.1 94.7 1.5Methamphetamine 86.4 10.8 95.2 6.0 81.6 6.7 80.8 1.7 Strychnine 90.6 6.986.8 8.0 51.2 11.8 87.9 5.0 Phentermine 88.4 8.8 94.9 2.9 85.2 7.6 94.33.4 MDEA ND ND 99.9 3.2 97.4 4.6 59.0 3.9 Heroin 97.7 8.7 87.4 2.3 89.08.1 82.8 7.1 Cocaine 96.3 2.7 100.2 3.1 101.5 3.4 94.5 3.0 Meperidine85.4 7.2 103.1 4.1 97.2 3.4 93.8 2.4 Trazodone 97.7 2.2 97.6 2.9 100.22.4 95.0 1.5 PCP 37.9 24.2 99.3 0.7 58.4 10.9 64.7 3.7 Nitrazepam 70.926.4 94.3 6.6 98.3 5.4 100.2 2.0 Oxazepam 119.7 19.5 94.2 1.1 99.9 4.696.0 2.3 Verapamil 108.3 11.9 97.9 3.7 82.6 3.6 97.6 2.9 Lorazepam 51.118.0 98.4 3.1 93.8 4.7 82.9 4.9 Methadone 90.1 12.2 94.7 3.4 61.8 10.794.8 4.6 Alprazolam 36.2 24.1 93.7 4.0 84.2 6.7 68.0 3.9 Temazepam 112.82.8 99.8 3.7 97.3 5.4 96.1 4.6 Proadifen 34.8 17.3 79.9 1.4 38.1 16.597.4 3.2 Diazeoam 91.0 1.9 100.5 1.7 102.1 3.6 35.5 2.0

Table 1. Recovery (% Rec.) and reproducibility (% RSD) results for drugsof abuse in human plasma. LLE and SLE used methyl t-butyl ether (MTBE)for extraction and silica materials were used as a stationary phase inan SLE workflow. Analytes were spiked at 10 ng/mL in replicates of six(n=6).

Example Analytical Results and Discussion Relative to Competitive SLESorbent

The inventors further performed analysis comparing several examples ofsynthetic silica particles according to this disclosure with acompetitive SLE product.

First Comparison of Three Example Types

In a first comparison, the inventors performed an analysis comparingthree synthetic silica particles (Agilent SLE material 1, 2, and 3) witha competitive SLE material. Results are shown in Tables 2 and 3 below.

Mean Peak Particle Surface Pore SLE sorbent Size (μm) Area (m²/g) Size(Å) Agilent SLE 102 29 >1000 Material 1 Agilent SLE 600 16 >1000Material 2 Agilent SLE 300 26 >1000 Material 3 Competitive SLE 114 43 85Sorbent

Table 2. Summary of physical properties for Agilent SLE materials andcompetitive SLE sorbent. Particle sizes of Agilent SLE Material 1 and acompetitive SLE sorbent were measured by Beckman Coulter particle sizeanalyzer. Particle sizes of Agilent SLE Material 2 and 3 were measuredunder Scanning Electronic Microscopy (SEM). Surface areas of allmaterials were measured using BET nitrogen adsorption analysis, wherethe pore sizes were determined by the peak position of adsorption curve.

TABLE 3 SLE sorbent Water Holding Capacity Gravity Flow Rate Agilent SLEMaterial 1 120%   1 mL/min Agilent SLE Material 2 100% 3-4 mL/minAgilent SLE Material 3 105% 3-4 mL/minTable 3. Summary of water holding capacity and flow rate properties forAgilent SLE materials and a competitive SLE material. Water holdingcapacity characterizes the amount of water the sorbent can hold under 15inch of Hg vacuum. High water holding capacity is preferred since alarger volume of aqueous sample can load onto a given weight of SLEsorbent. Gravity flow rate measurement were carried out by loading 20 mLwater onto 60 cc SLE tube (packed with 20 g sorbent materials) and theneluting 40 mL of Dichloromethane through the sorbent bed, where thegravity flow rate characterizes the flow rate of dichloromethane.Generally, a gravity flow rate of about 3-4 mL/min is preferred tobalance analyte recovery and elution time.

Glossary

The following glossary is provided to further aid understanding:

BET—Brunauer, Emmett and Teller

ICP—Inductively coupled plasma

LC—Liquid chromatography system

LLE—Liquid-liquid extraction

MS—Mass spectrometer

SEM—Scanning electron microscope

SLE—Supported-liquid extraction

QQQ—Triple quadrupole

While embodiments and applications have been shown and described, itwould be apparent to those skilled in the art having the benefit of thisdisclosure that many more modifications than mentioned above arepossible without departing from the inventive concepts disclosed herein.The invention, therefore, is not to be restricted except in the spiritof the appended claims.

What is claimed is:
 1. A method for extracting target analytes throughsupported liquid extraction (SLE), comprising: positioning sorbent mediain a container, wherein the sorbent media includes synthetic silicaparticles having a surface area less than about 30 m²/g and asubstantially uniform particle shape; loading an aqueous sample onto thesorbent media; equilibrating the loaded aqueous sample and the sorbentmedia to obtain a layer of the aqueous sample on the synthetic silicaparticles; eluting the obtained aqueous sample layer on the syntheticsilica particles with organic solvent to extract target analytes; andoutputting the extracted target analytes for analysis.
 2. The method ofclaim 1, further comprising pretreating the aqueous sample prior to theloading.
 3. The method of claim 1, wherein the synthetic silicaparticles have a particle size of less than about 150 μm, and furthercomprising applying a positive pressure or vacuum to initiate a flow ofthe aqueous sample through the sorbent media at a consistent flow rate.4. The method of claim 1, wherein the synthetic silica particles have aparticle size greater than about 200 μm, and further comprisinginitiating with gravity a flow of the aqueous sample through the sorbentmedia at a consistent flow rate.
 5. The method of claim 4, wherein thesorbent media consists essentially of the synthetic silica particles,and the positioning comprises positioning in the container the sorbentmedia consisting essentially of the synthetic silica particles.